Intratumoral CAVATAK (CVA21) and Ipilimumab in Patients With Advanced Melanoma (VLA-013 MITCI)

Sponsor

Viralytics (Industry)

Overall Status

Completed

CT.gov ID

NCT02307149

Collaborator

Providence Health & Services (Other)

Enrollment

Locations

Arm

Actual Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Open label, single arm study of intratumoral CVA21 and ipilimumab in advanced melanoma patients.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Biological: CAVATAK Drug: Ipilimumab	Phase 1

Detailed Description

Primary Objective:

To evaluate the safety and efficacy of CAVATAK (CVA21) administered intratumorally in combination with the approved dose and schedule of ipilimumab. Of particular interest is to estimate the overall response rate (ORR) in the subgroup of subjects with unresectable or metastatic stage III B/C or IV melanoma who have progressed on a single prior anti-PD-1 therapy.

Secondary Objectives:

Assess the clinical efficacy of ipilimumab in combination with intratumoral CVA21 in terms of:

Immune-related progression-free survival (irPFS) at 6 and 12 months,
Durable response rate (DRR),
1-year survival,
Overall survival (OS), and
Quality of life.

Assess the response of injected and non-injected melanoma lesions after CVA21 and ipilimumab.
Assess the time to initial response.

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A PHASE 1b STUDY OF INTRATUMORAL CAVATAK® (COXSACKIEVIRUS A21, CVA21) AND IPILIMUMAB IN PATIENTS WITH ADVANCED MELANOMA (VLA-013 MITCI)

Actual Study Start Date :

May 5, 2015

Actual Primary Completion Date :

Nov 5, 2019

Actual Study Completion Date :

Nov 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CAVATAK and ipilimumab CAVATAK intratumoral injection up to a total dose of 3 x 10⁸ TCID50 and ipilimumab intravenously at the recommended dose of 3 mg/kg	Biological: CAVATAK CAVATAK is a preparation of CVA21 Other Names: Coxsackievirus A21, CVA21 Drug: Ipilimumab Ipilimumab is a human cytotoxic T-lymphocyte antigen (CTLA-4)-blocking antibody indicated for the treatment of unresectable or metastatic melanoma Other Names: Yervoy®

Arm

Intervention/Treatment

Experimental: CAVATAK and ipilimumab

CAVATAK intratumoral injection up to a total dose of 3 x 10⁸ TCID50 and ipilimumab intravenously at the recommended dose of 3 mg/kg

Biological: CAVATAK

CAVATAK is a preparation of CVA21

Other Names:

Coxsackievirus A21, CVA21

Drug: Ipilimumab

Ipilimumab is a human cytotoxic T-lymphocyte antigen (CTLA-4)-blocking antibody indicated for the treatment of unresectable or metastatic melanoma

Other Names:

Yervoy®

Outcome Measures

Primary Outcome Measures

Response [106 days]
Best response of complete response (CR) or partial response (PR)

Secondary Outcome Measures

DRR [lasting 26 weeks or longer]
Durable Response Rate
PFS [At 6 and 12 months]
Progression-Free Survival
OS [Through study completion, an average of 2 years]
Overall

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with unresectable or metastatic stage III B/C or IV melanoma. Patients enrolled under this version of the protocol must also have progressed on prior anti-PD-1 therapy, according to RECIST 1.1 criteria. Patients who progressed within 3 months of treatment start are excluded.
Patients must have at least one cutaneous or subcutaneous tumor, measuring 0.5 to 5.0 cm in the longest diameter, or a palpable lymph node. At least one tumor must qualify as an index lesion that can be accurately and reproducibly measured in two dimensions for which the longest diameter is .10 mm (.15 mm in short axis diameter [SAD] for lymph nodes), and be amenable to intratumoral injection.
Histological confirmation of melanoma will be required by previous biopsy or cytology.
Patients who have received prior ipilimumab treatment for metastatic melanoma are not eligible.
Patients with ≤ 3 visceral metastases (excluding pulmonary lesions), with no lesions

3.0 cm. Patients with substantial tumor burden of non-measurable disease may not be good candidates for an immunotherapy and should be discussed with the Medical Monitor.

ECOG performance status of 0-1.

Key Exclusion Criteria:

Patients with tumors to be injected lying close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigator, could cause occlusion or compression in the case of tumor swelling or erosion into a major vessel in the case of necrosis. Patients with lesions in mucosal areas (vulvar, anus, oral cavity, etc.), are eligible, as long as the subject has at least one lesion suitable for injection; consult Medical Monitor for confirmation.
Patients with active, known or suspected autoimmune disease except for autoimmune thyroiditis or vitiligo. Thyroiditis patients must be asymptomatic, on adequate thyroid replacement and have normal thyroid function tests.
Patients with active colitis or immune-mediated colitis that has not resolved to grade 1 or less.
Patients with untreated brain metastases. Patients with treated brain metastases who are off corticosteroids for at least two weeks and who demonstrate control of brain metastases with follow-up imaging 4 or more weeks after initial therapy are eligible.
Patients previously treated with CVA21.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center,	Duarte	California	United States	91010
2	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
3	The Angeles Clinic & Research Institute	Los Angeles	California	United States	90025
4	John Wayne Cancer Institute	Santa Monica	California	United States	90404
5	Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
6	Advocate Health, SC	Park Ridge	Illinois	United States	60068
7	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
8	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
9	Atlantic Melanoma Center	Morristown	New Jersey	United States	07960
10	Providence Portland Medical Center	Portland	Oregon	United States	97213
11	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112